Platelets play an important role in normal hemostasis and in atherosclerosis and arterial thrombosis. Experiments have shown that there is a reaction between the circulating platelets and the collagen when the subendothelium is exposed, with subsequent aggregation of the platelets and release of certain intracellular components. The overall goal of the proposed project is the further elucidation of the interaction of platelets with collagen in vitro. This will be done by the following approach: (1) The binding of collagen to platelets will be investigated. Binding studies with 14C glycine collagen and with hydroxyproline as a marker for collagen will be attempted with intact platelets and with platelet membranes isolated by sucrose density ultracentrifugation. In all studies degree of microfibril formation or "polymerization" of the tropocollagen molecule will be monitored by spectrophotometry at 290 nm, viscometry, and electronmicroscopy. (2) Solubilization, isolation, and characterization of the collagen receptor site of human platelets will be attempted. (3) Further requirements of the collagen microfibril for platelet aggregation and the release reaction will be studied. Polar groups of collagen will be modified and the degree of quaternary structure of the modified collagen determined and correlated with the ability of the collagen to cause platelet aggregation and release. (4) The coagulant activity of platelets generated by collagen and factor XI will be studied and related to the quaternary structure of the collagen. (5) In vitro collagen binding and coagulant activity of platelets will be studied in patients with platelet hypofunction (platelet release abnormality, drugs such as aspirin, dipyridamole, and sulfinpyrazone), and platelet hyperfunction (hyperbetalipoproteinemia; myocardial infarction, transient ischemia attack, and atherosclerosis).